NICE approves first immunotherapy combination for advanced bowel cancer patients with rare MSI-H/dMMR mutation

Bristol Myers Squibb (BMS) today announced that the National Institute for Health and Care Excellence (NICE) has issued a Final Appraisal Document (FAD) recommending the combination of nivolumab plus ipilimumab for advanced colorectal (bowel) cancer patients with the rare MSI-H/dMMR mutation, after they have previously failed fluoropyrimidine-based chemotherapy.  This is the first immunotherapy combination approved in the UK for this patient group,1 who have a form of advanced bowel cancer characterised by rare gene mutations known as high microsatellite instability (MSI- H) or mismatch repair deficiency (dMMR), which affect how the cancer grows.

“Advanced bowel cancer with the rare MSI-H/dMMR mutation can be difficult to treat,” said Genevieve Edwards, Chief Executive at Bowel Cancer UK. “If chemotherapy fails then this patient population has had limited treatment options, so we welcome the NICE decision to make this combination of nivolumab with ipilimumab available to them.”

The NICE recommendation is based on data from the ongoing Phase II Checkmate-142 study, which showed that the combination of nivolumab plus ipilimumab can potentially offer long progression-free survival (PFS) and overall survival (OS).1 An objective response rate of 65% after a follow up period of 51 months was seen with the combination treatment. 1 The decision from NICE offers a new treatment option for patients with bowel cancer after chemotherapy has failed, for whom there are currently limited treatment options.

“At Bristol Myers Squibb we are committed to bringing our innovative medicines to patients across the UK and Ireland,” said Dr Hubert Bland, Executive Medical Director UK and Ireland, Bristol Myers Squibb. “We are grateful to the hospitals and patients involved in the trials that have helped bring this immunotherapy combination to patients with advanced bowel cancer.”

Cancer which originates in the colon or rectum and has spread to other organs of the body is called advanced bowel cancer or metastatic colorectal cancer.  5,6 There are around 42,300 new cases of bowel  Page 2/4 © 2021 Bristol Myers Squibb Company | 7356-GB-2100371 | June 2021 cancer in the UK every year, of which over half are diagnosed at a late stage.  7 When bowel cancer is diagnosed at its latest stage, only 10% of people will survive for five years or more.7 Approximately 4% of patients with metastatic colorectal cancer show high MSI, where errors that occur during DNA replication are not corrected by the body’s normal DNA repair system.2,3 DNA MMR deficiency results in MSI mutations, tumour development and progression.

About nivolumab

Nivolumab is a programmed death-1 (PD-1) immune checkpoint inhibitor that is designed to harness the body’s own immune system to help restore anti-tumour immune response.8 By harnessing the body’s own immune system to fight cancer, nivolumab has become an important treatment option across multiple cancers. 

About ipilimumab

Cancer cells may exploit “regulatory” pathways, such as checkpoint pathways, to hide from the immune system and shield the tumour from immune attack.9 Ipilimumab is a monoclonal antibody and immune checkpoint inhibitor that targets immune checkpoint pathways that regulate T-cell differentiation and function.

About CheckMate -142

CheckMate -142 included a multicentre, non-randomised, open-label cohort investigating nivolumab plus ipilimumab in patients with mismatch repair deficient (dMMR) or microsatellite instability–high (MSI-H) metastatic colorectal cancer (mCRC) whose disease had progressed during or after prior treatment with fluoropyrimidine, oxaliplatin and irinotecan.

In this combination cohort, patients received nivolumab 3 mg/kg with ipilimumab 1 mg/kg every three weeks for four doses, followed by nivolumab 3 mg/kg as a single agent every two weeks until disease progression, death, or unacceptable toxicity.

76% of patients had two or more prior lines of therapy (N=119). 12 At a median follow-up of 25.4 months, ORR and disease control rates were 58% and 81%, respectively. 12 Complete response (CR) rate increased with long-term follow-up from 3% (13.4 months) to 6% (25.4 months).12 Median duration of response was not reached, with 68% of responses ongoing at data cut-off.12 At 24 months, PFS and OS rates were 60% and 74%, respectively. 12 Grade 3–4 treatment-related adverse events (TRAEs) occurred in 31% of patients; 10% (Grade 3–4) and 13% (any Grade) of patients had TRAEs leading to discontinuation.